The overall objectives of this research are three fold: to clearly establish if muscarinic receptors exist on adrenergic and dopaminergic neurons in the CNS and if their activation results in a decrease in the release of these two neurotransmitters following physiological and pharmacological stimulation. This will be done by: 1) studying the effect of cholinergic agents on the release of newly synthesized NE and DA IN VITRO using brain slices, 2) studying the effect on the release of newly synthesized NE and DA from synaptosomes and, 3) studying the effect of the release of newly synthesized NE and DA IN VIVO. The second objective is to determine the physiological significance of this process. This will be done by: 1) determing if dual adrenergic- cholinergic innervation is necessary, 2) studying the interaction of the muscarinic-inhibitory receptors with the two receptors involved in local feed-back control of NE release (presynaptic alpha and presynaptic prostaglandin receptors), 3) determining if muscarinic agonists alter the release of other neurotransmitters and, 4) determining if other neurotransmitters have a similar presynaptic action. The third objective is to obtain information on the mechanism of this inhibitory action. This will be done by mainly concentrating on the role of cyclic nucleotides. The main significance of such a mechanism is that it may represent a new and extremely important site of control by which monoaminergic transmission is modulated and controlled in the nervous system and an important site of interaction between cholinergic- monoaminergic neurons. It may represent an important basic mechanism in the regulation of neurotransmission.